The transcription factor E2F, the principal target of the tumor suppressor pRB, plays crucial roles in cell proliferation and tumor suppression. In almost all cancers, pRB function is disabled, and E2F activity is enhanced. To specifically target cancer cells, trials have been undertaken to suppress enhanced E2F activity to restrain cell proliferation or selectively kill cancer cells, utilizing enhanced E2F activity. However, these approaches may also impact normal growing cells, since growth stimulation also inactivates pRB and enhances E2F activity. E2F activated upon the loss of pRB control (deregulated E2F) activates tumor suppressor genes, which are not activated by E2F induced by growth stimulation, inducing cellular senescence or apoptosis to protect cells from tumorigenesis. Deregulated E2F activity is tolerated in cancer cells due to inactivation of the ARF-p53 pathway, thus representing a feature unique to cancer cells. Deregulated E2F activity, which activates tumor suppressor genes, is distinct from enhanced E2F activity, which activates growth-related genes, in that deregulated E2F activity does not depend on the heterodimeric partner DP. Indeed, the ARF promoter, which is specifically activated by deregulated E2F, showed higher cancer-cell specific activity, compared to the E2F1 promoter, which is also activated by E2F induced by growth stimulation. Thus, deregulated E2F activity is an attractive potential therapeutic tool to specifically target cancer cells.
Statins have recently been reported to have anticancer effects and can be used as anticancer agents via drug repositioning. In reverse transcription quantitative polymerase chain reaction (RT-qPCR), the internal reference gene itself must not be affected by any experimental conditions. Since statins are considered to have a wide range of effects on cells via inhibition of the mevalonate pathway, there is a high possibility that statins might vary the expression of internal reference genes, thereby misleading the obtained gene expression data. The present study evaluates the expression stability of the internal reference genes. Statin-sensitive cancer cells (lung cancer-derived HOP-92, prostate cancer-derived PC-3, and melanoma-derived SK-MEL-5 and MDA-MB-435) and statin-resistant cancer cells (lung cancer-derived NCI-H322M and prostate cancer-derived DU-145) were used for the analysis. Atorvastatin was administered at seven different concentrations (0–30 µM). RT-qPCR was performed for the 15 internal reference genes, and then five algorithms were used to evaluate the stability of internal reference genes. Both statin-sensitive and statin-resistant cancer cells showed that atorvastatin affected certain internal reference genes in a dose-dependent manner. The effect of statins on internal reference genes is dependent on the cancer cell type, suggesting that caution should be exercised when comparing expression between cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.